Sean Eddy

Professor of Molecular and Cellular Biology and of Applied Mathematics

Harvard University
Biological Laboratories, Room 1008B
16 Divinity Ave
Cambridge, MA 02138


Lab Size: Between 5 and 10


We are interested in deciphering the evolutionary history of life by comparative analysis of genome sequences. We develop computational algorithms and software tools for genome sequence analysis, including the HMMER and Infernal software packages for identifying distant homologs of biological sequence families. We rely on Bayesian probabilistic inference approaches, including hidden Markov models(stochastic regular grammars) for primary structure analysis of proteins and DNA, and stochastic context-free grammars for RNA  
secondary structure and sequence analysis.                                                         

We have a special interest in RNA.  The "ancient RNA world" hypothesis says that an ecosphere of RNA-based life preceded protein/DNA based life. Some RNA genes that we see today are thought to be ancient relics of the RNA world. By studying modern RNAs, we may learn something about the origins of life. But in addition, we and others have also been finding that the RNA World model is pessimistic in a sense: far from being a few scattered relics, RNAs are in widespread use in modern organisms in a variety of roles. We have argued for a “modern RNA world" hypothesis, that many of the RNAs we see today are modern inventions, highly adapted to regulatory roles in complex organisms.                                                                                         

Most recently, our laboratory has begun looking for ways to study one of the great mysteries in biology: how a relatively small genome manages to specify biological complexity, especially something as complex as what we see in the neural circuits of a brain.  This is an area where molecular evolutionary biology still largely lacks quantitative language for asking precise questions.  As one way forward in this difficult frontier, we collaborate with neuroscientists working on the molecular regulatory specification of neural cell types in fly, worm, and mouse.                                                         


Eddy, S.R. Computational analysis of conserved RNA secondary structure in transcriptomes and genomes. Annu Rev Biophys. 2014;43:433-56. doi: 10.1146/annurev-biophys-051013-022950.

E. P. Nawrocki, S. R. Eddy. Infernal 1.1: 100-fold Faster RNA Homology Searches. Bioinformatics, 29:2933-2935, 2013.

G. L. Henry, F. P. Davis, S. Picard, S. R. Eddy. Cell Type-Specific Genomics of Drosophila Neurons. Nucleic Acids Research, 40:9691-9704, 2012.

S. R. Eddy. Accelerated profile HMM searches. PLoS Comp. Biol., 7:e1002195, 2011.

S. Jung, E. C. Swart, P. J. Minx, V. Magrini, E. R. Mardis, L. F. Landweber, S. R. Eddy. Exploiting Oxytricha trifallax nanochromosomes to screen for noncoding RNA genes. Nucleic Acids Research, 39:7529-7547, 2011.